Myasthenia Gravis: etiology, pathophysiological & therapeutic approaches
Myasthenia gravis is an autoimmune diseases; diseases that affect more than 5% of the population. These are multifactorial diseases involving genetic predispositions, hormonal implication, dysfunctions of the immune system, and are triggered by unidentified factors. Myasthenia gravis is due to autoantibodies directed against components of the neuromuscular junction, mainly the acetylcholine receptor (AChR, 85% of cases) but sometimes also against the muscle-specific tyrosine kinase receptor (MuSK) or the LRP4 protein interacting with agrin. These autoantibodies reduce the efficiency of neuromuscular transmission and lead to abnormal muscle fatigability.
The thymus is most likely the site of initiation of myasthenia gravis with anti-AChR antibodies. Histological abnormalities of the thymus are very common: 50-60% of the patients present follicular hyperplasia with ectopic germinal centers, and 10-15% of the patient present a tumor of the thymus (Thymoma). Thymectomy is one of the treatments proposed to these patients.
The research projects developed by the team aim to understand the etiological and pathophysiological mechanisms involved in myasthenia gravis and to propose new therapeutic approaches. More specifically, our objectives are to:
- Elucidate the etiological mechanisms involved in autoimmunity by analyzing the impact of sex hormones and endocrine disruptors in central tolerance processes.
- Understand the cellular and molecular mechanisms at the origin of thymus inflammation and remodeling observed in patients.
- Study the immunoregulatory defects in myasthenia gravis patients by studying the functional phenotype of peripheral and thymic cells by mass cytometry (CyTOF).
- Develop new therapeutic approaches. In this context, we are studying the immunomodulatory and therapeutic potential of mesenchymal stem cells, and the potential of molecules interfering with inflammatory pathways.
- Search for circulating biomarkers to follow the evolution of the disease and the response to treatments.
| Name | Position | ORCID |
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- Alexandra Bayer Wildberger, Natalia Pinzon, Axel You, Frédérique Truffault, Aurélien Corneau, et al.. Cell therapy approaches for Myasthenia gravis: in vitro and in vivo evaluations of conditioned mesenchymal stem cells. 12th Japanese-French Workshop, Sep 2022, Giverny, France. ⟨hal-03824310⟩
- Rozen Le Panse. Role of endogenous nucleic acids in interferon type 1 signature in early-onset AChR Myasthenia Gravis. 14th MGFA International Conference On Myasthenia And Related Disorders, May 2022, Miami (FL), United States. ⟨hal-04008218⟩
- Frédérique Truffault, Jérôme van Wassenhove, Elie Fadel, Francis Bolgert, Sophie Demeret, et al.. Novel biomarkers associated with autoimmune Myasthenia Gravis: a pilot study using two different proteomic approaches. 14th MGFA International Conference On Myasthenia And Related Disorders, May 2022, Miami, United States. ⟨hal-03853740⟩
- Sonia Berrih-Aknin. Biomarker response to thymectomy. 14th MGFA International Conference On Myasthenia And Related Disorders, May 2022, Miami (FL), United States. ⟨hal-04008400⟩
- Anne-Charlotte Lefranc, Samy Hamadache, Lucie Garnier, Frédérique Truffault, Elie Fadel, et al.. MAY IL-17 PLAY A ROLE IN SKELETAL MUSCLE IN PATHOPHYSIOLOGICAL MECHANISM IN AUTOIMMUNE MG?. 14th MGFA International Conference On Myasthenia And Related Disorders, May 2022, Miami, United States. ⟨hal-03844178⟩
- Alexandra Bayer Wildberger, Natalia Pinzon, Axel You, Frédérique Truffault, Aurélien Corneau, et al.. Conditioned Mesenchymal Stromal Cells as tools for immunomodulation in Myasthenia Gravis. 14th international MGFA Conference on Myasthenia and Related Disorders, May 2022, Miami, United States. ⟨hal-03824297⟩
- Julien Verdier, Edouard Hemery, Odessa-Maud Fayet, Frédérique Truffault, Aurélien Corneau, et al.. Characterization of circulating immune cells in Myasthenia Gravis by mass cytometry revealed dysregulation on innate immune cells. 14th MGFA International Conference On Myasthenia And Related Disorders, May 2022, Miami, United States. ⟨hal-03853709⟩
- Jose Adolfo Villegas, Nadine Dragin. Blocking IL-23 ameliorates Myasthenia Gravis. 14th MGFA International Conference On Myasthenia And Related Disorders, May 2022, Miami, United States. ⟨hal-03844191⟩
- Edouard Hemery, Frédérique Truffault, Julien Verdier, Sophie Demeret, Sonia Berrih-Aknin, et al.. Decrease in non-classical monocytes in Myasthenia Gravis patients. 14th MGFA International Conference On Myasthenia And Related Disorders, May 2022, Miami, United States. ⟨hal-03853647⟩
- Cloé Payet, Axel You, Odessa-Maud Fayet, Nadine Dragin, Sonia Berrih-Aknin, et al.. Myasthenia Gravis: An Acquired Interferonopathy?. Cells, 2022, 11 (7), pp.1218. ⟨10.3390/cells11071218⟩. ⟨hal-03641038⟩
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